What is the recommended diagnostic and treatment approach for a patient suspected of having leukemia or lymphoma?

From the Guidelines

The recommended approach for a patient suspected of having leukemia or lymphoma begins with a thorough clinical evaluation including a complete blood count with differential, comprehensive metabolic panel, and lactate dehydrogenase level, as stated in the guidelines by the National Comprehensive Cancer Network 1. Definitive diagnosis requires tissue sampling—bone marrow biopsy and aspiration for leukemia, or lymph node biopsy for lymphoma, with the use of flow cytometry and immunohistochemistry to establish the diagnosis and subtype of the disease 1. Imaging studies such as CT, PET, or MRI scans help determine disease extent and staging, and are essential for guiding treatment decisions 1. Once diagnosed, treatment is typically directed by a hematologist-oncologist and may include chemotherapy regimens (such as CHOP for non-Hodgkin lymphoma or ABVD for Hodgkin lymphoma), targeted therapies (like rituximab for CD20-positive lymphomas or tyrosine kinase inhibitors like imatinib for chronic myeloid leukemia), immunotherapy, radiation therapy, or stem cell transplantation, with treatment protocols highly individualized based on the specific disease subtype, molecular markers, patient age, comorbidities, and disease stage 1. Some key points to consider in the diagnostic workup include:

• The use of core needle biopsy or excisional lymph node biopsy for diagnosis, with fine-needle aspiration biopsy being insufficient except in unusual circumstances 1
• The importance of immunophenotyping and cytogenetic analysis in establishing the diagnosis and subtype of the disease 1
• The need for a thorough clinical evaluation, including a complete blood count with differential, comprehensive metabolic panel, and lactate dehydrogenase level, as well as imaging studies to determine disease extent and staging 1
• The importance of early referral to a hematologist-oncologist, as these diseases often require urgent intervention, particularly acute leukemias which may need immediate hospitalization and treatment initiation within days of diagnosis 1. Supportive care including infection prophylaxis, growth factors like filgrastim to support neutrophil counts, and transfusion support is essential during treatment, and treatment protocols should be highly individualized based on the specific disease subtype, molecular markers, patient age, comorbidities, and disease stage 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). 1.2 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with 17p deletion IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with 17p deletion.

The recommended diagnostic approach for a patient suspected of having leukemia or lymphoma is not directly stated in the provided drug label. However, for treatment, ibrutinib (IMBRUVICA) is indicated for adult patients with:

• Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
• CLL/SLL with 17p deletion 2 A definitive diagnosis of leukemia or lymphoma should be made prior to initiating treatment with ibrutinib.

From the Research

Diagnostic Approach

• The diagnosis of leukemia or lymphoma is typically confirmed by further examination of the bone marrow or peripheral blood 3, 4.
• A complete blood count usually reveals leukocytosis and other abnormally elevated or depressed cell lines 3.
• Patients with suspected leukemia should be referred promptly to a hematologist-oncologist 3, 4.
• Molecular diagnostics, such as polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH), play an essential role in the diagnostic panel for acute leukemia 5.

Treatment Approach

• Treatment may include chemotherapy, radiation, monoclonal antibodies, or hematopoietic stem cell transplantation 3, 4.
• Targeted molecular therapy, such as tyrosine kinase inhibitors (TKIs), may be used in specific cases, such as BCR-ABL positive acute lymphoblastic leukemia (ALL) 5.
• For chronic lymphocytic leukemia (CLL), treatment options include a combination of the B-cell lymphoma 2 (BCL2) inhibitor venetoclax with obinutuzumab, monotherapy with inhibitors of Bruton tyrosine kinase (BTK) such as ibrutinib and acalabrutinib, or chemoimmunotherapy 6.
• Patients with a del(17p) or TP53 mutation are usually resistant to chemotherapy and should be treated with targeted agents 6.

Prognosis and Monitoring

• Five-year survival rates are highest in younger patients and in patients with chronic myelogenous leukemia or chronic lymphocytic leukemia 3, 4.
• Leukemia survivors should be monitored closely for secondary malignancies, cardiac complications, and endocrine disturbances such as metabolic syndrome, hypothyroidism, and hypogonadism 3.
• The residual leukemic cell load can be monitored by highly sensitive quantitative PCR techniques ("real-time PCR") 5.
• The CLL international prognostic index integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL 6.